Here’s a little question to see if you remember the different causes of conjugated and unconjugated bilirubinemia
While examining the gums of a 25 year old patient, a yellowish discoloration of the oral mucosa and sclera is noted. Laboratory tests show a significant increase in unconjugated bilirubin. Which of the following disorders is most likely the cause of this patient’s abnormalities?
A. A stone in the bile duct
B. Carcinoma of the head of the pancreas
C. Pancreatic pseudocyst
D. Sickle cell disease
E. Hepatocellular carcinoma
Let’s review a little before we get to the question.
Bilirubin is a breakdown product of heme (which, in turn is part of the hemoglobin molecule that is in red blood cells). It is a yellow pigment that is responsible for the yellow color of bruises, and the yellowish discoloration of jaundice.
When old red cells pass through the spleen, macrophages eat them up and break down the heme into unconjugated bilirubin (which is not water soluble). The unconjugated bilirubin is then sent to the liver, which conjugates the bilirubin with glucuronic acid, making it soluble in water. Most of this conjugated bilirubin goes into the bile and out into the small intestine. (An interesting aside: some of the conjugated bilirubin remains in the large intestine and is metabolized into urobilinogen, then sterobilinogen, which gives the feces its brown color! Now you know.)
So: if you have an increase in serum bilirubin, it could be either because you’re making too much bilirubin (usually due to an increase in red cell breakdown) or because you are having a hard time properly removing bilirubin from the system (either your bile ducts are blocked, or there is a liver problem, like cirrhosis, hepatitis, or an inherited problem with bilirubin processing).
The lab reports the total bilirubin, and also the percent that is conjugated vs. unconjugated. If you have a lot of bilirubin around and it is mostly unconjugated, that means that it hasn’t been through the liver yet – so either you’ve got a situation where you’e got a ton of heme being broken down (and it’s exceeding the pace of liver conjugation), or there’s something wrong with the conjugating capacity of the liver (like a congenital disorder where you’re missing an enzyme necessary for conjugation – for example, Gilbert syndrome).
If you’ve got a lot of bilirubin around and it’s mostly conjugated, that means it’s been through the conjugation process in the liver – so there’s something preventing the secretion of bilirubin into the bile (like hepatitis, or biliary obstruction), and the bilirubin is backing up into the blood.
Back to our question. Let’s go through each answer and see what kind of hyperbilirubinemia these disorders would cause.
A. A stone in the bile duct. If big enough, a stone here could block the excretion of bilirubin into the bile. The bilirubin would already be conjugated, so this would be a conjugated bilirubinemia.
B. Carcinoma of the head of pancreas. This could also cause biliary obstruction, similar to A. (An important aside: it’s nice when pancreatic carcinomas announce themselves this way, because it may allow for earlier detection of the tumor. Unfortunately, this is uncommon. Pancreatic adenocarcinoma is usually silent until the tumor is very large and possibly metastatic.)
C. Pancreatic pseudocyst. Same idea as A and B.
D. Sickle cell disease. Sickle cell anemia is a type of hemolytic anemia. It could be a cause of unconjugated bilirubinemia, if the hemolysis is massive enough. If it’s just a low level of hemolysis, the liver could probably keep up, and you’d get a conjugated hyperbilirubinemia.
E. Hepatocellular carcinoma. This would fall into the category of blocking excretion of bilirubin. The bilirubin would already be conjugated – so this would be a conjugated hyperbilirubinemia.
So: since A, B, C and E produce only conjugated hyperbilirubinemia, the answer is D, sickle cell disease.
Great job that was really simple and clearly explained Thankyou
stumbled upon this and am truly amazed! thank you!
was reviewing hgb breakdown n different hemolytic processes from hematology course I took last yr when I found this site. now this is in my bookmarks.
very helpful. simple and concise. thanks a lot!
Great topic!
Just a heads-up: I had “Crigler-Najjar Syndrome” on a test recently…an infant with high unconj. bilirubin.
Dubin-Johnson and Rotor syndrome too; Don’t let these catch you off guard like they did me, haha.
Good syndromes to remember! Thanks.
Great job! Very helpful site..love it
Thank you so much for such a concise ans.
Just awesome! Thanks a lot for the concise and helpful info. I really like it.
I know I have reviewed Crigler-Najjar syndrome, and Dubin Jhonson syndromes, but I really would like to ask you to explain them as well as Rotor once again exactly like what you did on conju vs. unconj bilirubinemia.
Thanks,
Thanks!! I wrote a post on Crigler-Najjar, Gilbert, Dubin-Johnson, and Rotor syndromes etc. that might be useful.
Thank you for explaining conjugated vs. unconjugated bilirubin. I’m studying for my finals and it helps when you understand the mechanisms involved in liver disease instead of meorizing the different types.
Thank you so much for the explanation. Very clear indeed.
Nice work! Thank you. I’ve been having a hard time differentiating them. You’ve just put me to rest on this issue.
thats was a good recap…..u’ve really helped
Plain & Simple…..excellent!!!!
Thank you so much for breaking down this information and making it easy to understand.Understanding the concept is so much better than rote memorization. It is much easier to answer any question once you understand the concept.
great explanation..kudos..was asked if sickle cell anemia would be able to come down with conjugated hyperbilirubinemia? am glad the answer is obvious..me lv
thanks for this website, Dr. Krafts! more power!
This came up as one of my choices during a search on conjugation of bilirubin…Wow! Love it! Clear and easy to understand. Many thanks!!!
Hey, that’s great! I’m glad you found it useful!
having a test on this in a few days!this is so useful! thanks 😀
Great!! Hope it helps. We just had a test too on the same material in my class.
Concise and well explained
Thanks..I just wanted a quick review and I stumbled upon your site on a Bing search…very well written. 🙂 Second time in two days that Bing has brought me to your site. I also signed up for your email…yesterday!
Welcome!! I hope you find what you need here!
thanks! alot, very happy when i saw because it took much time to differentiate them.
Great! Glad to be able to help.
Hi, in hepatocellular carcinoma, the functional hepatocytes are constantly being crowded out and destroyed by the tumour growth, so would that make both conjugated and unconjugated bilirubin high as well since there are actually lesser functional cells to conjugate the bilirubin?
Good question. The liver has a very big reserve and is able to function well even if you remove a big portion (for example, you can remove a whole lobe to donate to another person, and the bili will normalize!). So unless the tumor is gigantic, the destruction/removal of normal liver cells probably won’t in and of itself lead to an unconjugated hyperbilirubinemia. If you see a hyperbilirubinemia because of a tumor, it’s usually a conjugated hyperbilirubinemia due to the tumor’s obstruction of biliary excretion. Check out page 841 of Robbins (especially table 18-2).
Short&well explained. Nicely done
WELL DONE!
I UNDERSTOOD EVERY THING YOU HAVE WRITTEN.
THANKS.
thnx u hv explianed well
thankyou very much sir for providing valuable information througu website. It is really gives lot to learn about our body organs functioning and we can help through sharing this to needy people around us. thankyou very much once again.
woohoo! med student…revising…couldn’t remember the whole bilirubin situ…found your blog…saved the day! 🙂
Great!! That made my life easier thank you!!
Very clear, thanks!
thank you sir ,, its fantastic .
Thank you so much. This post helped me a lot :)!
Sou Brasileiro e na tradução que eu fiz não ficou claro qual a resposta correta.
Oh! Sorry – the answer is D, sickle cell disease.
Just for completeness – HCC is not commonly associated with raised Br. So regardless of its conj/unconj status (and it is nearly always an obstructive picture) it is only likely to be seen in 1 in 10 patients presenting with HCC.
Thanks Dr. L!
this helps a lot! I can easily understand this, thank you!
Thank you so much for this incredibly thorough, yet easy to understand, answer! I hope you are considering teaching at some point in your career 🙂
Very helpful in understanding direct and indect bilirubin. Thanks!
Thanks alot
Thanks so much! It really helped me in better understanding in of both types of bilirubin. Keep it up!
Thank you for the clear explanation.
Prior to reading your explanation, my answer was actually D (Sickle Cell Disease/Hemolytic Anemia) or E(HCC). More of E actually since I thought that there must be significant breakdown of RBC/accumulation of bilirubin so much so as to overwhelm the liver conjugation system so as to produce unconjugated bilirubinemia.
I chose HCC because I thought that the cancer would result in loss of function of the normal liver conjugation function – resulting in unconjugated bilirubinemia?
Is that possible? Or does HCC always produce conjugated bilirubinemia due to obstruction rather than loss of function?
I think a tumor is more likely to produce obstruction than loss of function, because the liver has quite a big reserve. You have to destroy a large part of it to see a drop in function – and unless the tumor is really replacing a majority of the liver, there would likely be enough liver tissue left to manage the bilirubin. I wouldn’t say that HCC never leads to loss of function (because we almost never say never/always in pathology) – but I would say in the majority of cases, HCC leads to obstruction rather than loss of function. I hope that helps a bit.
I can’t thank u enough, honestly